Concurrently, the combined regimen enhanced their respective anticancer effects by inhibiting the key genes HDAC10 and BCL-xL. Taken together, venetoclax combined with chidamide presents a potent anticancer strategy in preclinical models of t-FL and merits further exploration in clinical trials to validate its effectiveness and safety for treating t-FL.

Together, these findings provide a rationale for the combination of HPV vaccine, NHS-IL12, and Entinostat in the clinical setting for patients with HPV16-associated malignancies.

P2, N=33, Not yet recruiting, Tianjin Medical University Cancer Institute and Hospital

This study is the first to demonstrate that HDAC inhibition enhances NK cell-mediated cytotoxicity in DMG. Combining HDAC inhibition with NK cell therapy represents a promising therapeutic strategy for treating DMG by targeting NKG2A-HLA-E axis.

P2, N=58, Completed, National Cancer Institute (NCI) | Active, not recruiting --> Completed

P3, N=224, Not yet recruiting, Chipscreen Biosciences, Ltd.

These findings suggest that the BTG1/BECN1/ATG5 signaling axis plays a critical role in enhancing autophagy and reversing Rituximab resistance. The combination of Chidamide and Rituximab presents a promising therapeutic strategy, offering new insights into overcoming drug resistance in DLBCL.

Topical entinostat plus imiquimod immunotherapy blocked BCC development in mice. Collectively, our findings demonstrate that low BCC immunogenicity is associated with a stem-like quiescent program preserved in the tumor cells, which can be blocked to enable BCC immunotherapy.

Our findings illustrate the suppressive effect of CAP treatment on endometrial cancer and uncover a novel regulatory mechanism mediated by CAP. Specifically, CAP modulates the ferroptosis pathway through the HDAC3/H3K18la/p53 axis, presenting a novel therapeutic approach for endometrial cancer treatment.

P2, N=58, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Mar 2025 --> Mar 2026

Combined inhibition of class I HDACs and LSD1 potently increases SSTR2 expression and consequently radioligand binding and might thus be a putative strategy to improve the outcome of PRRT therapy in patients with NETs.

Short-term systemic pharmacological inhibition of HDACs using the HDACi Entinostat in a premalignant ALCL mouse model postponed or even abolished lymphoma development, despite high expression of the NPM::ALK fusion oncogene...Our findings underscore the tumor-suppressive function of HDAC1 and HDAC2 in T cells during ALCL development. Nevertheless, systemic pharmacological inhibition of HDACs could still potentially improve current therapeutic outcomes.

P=N/A, N=30, Recruiting, Dongguan Kanghua Hospital; Dongguan Kanghua Hospital

P2, N=50, Recruiting, Fujian Medical University Union Hospital; Fujian Medical University Union Hospital

P2, N=42, Not yet recruiting, The First Affiliated Hospital of Soochow University; The First Affiliated Hospital of Soochow University

P2, N=223, Not yet recruiting, The Affiliated Hospital of Qingdao University; the Affiliated Hospital of Qingdao University

P1/2, N=55, Active, not recruiting, National Cancer Institute (NCI) | Recruiting --> Active, not recruiting | N=107 --> 55

P1/2, N=12, Terminated, Henan Cancer Hospital | N=28 --> 12 | Trial completion date: Jan 2027 --> Feb 2025 | Recruiting --> Terminated; The clinical development of parsaclisib was stopped by it's manufacturer.

P1, N=28, Completed, National Cancer Institute (NCI) | Active, not recruiting --> Completed

P2, N=128, Not yet recruiting, Li Zhiming

ENT-treated CAR-NK cells exhibited prolonged persistence and more significant tumor reduction in an MM tumor-bearing mouse model, highlighting the therapeutic potential of HDACi-treated CAR-NK cells. This study provides the first evidence that HDAC inhibitors can sustain CAR expression in CAR-NK cells in a promoter-dependent manner, potentially enhancing anti-tumor efficacy in multiple myeloma and underscoring the possible need for further clinical evaluation.

P2, N=148, Recruiting, The First Affiliated Hospital with Nanjing Medical University

P1/2, N=191, Completed, Syndax Pharmaceuticals | Phase classification: P1b/2 --> P1/2

This combination treatment also increased CD8+T cell tumor infiltration in the AOM-DSS CRC model, thereby leading to an anti-tumor immune response. Therefore, the combination of MS275 and anti-PD-1 immunotherapy represents a potential strategy for low PD-L1 expression tumors and should be considered a promising treatment approach for colon cancer.

P2, N=22, Recruiting, Tianjin Medical University Cancer Institute and Hospital | Not yet recruiting --> Recruiting | Initiation date: Sep 2024 --> May 2025

Between October 2021 and July 2023, 24 patients aged 41 to 88 years (median, 73.4 years) who had undergone prior therapies, including intensive chemotherapy (79.2%) and mogamulizumab immunotherapy (79.2%), received tucidinostat. Treatment-related adverse events were mainly hematologic but were managed over the course of treatment. Our findings indicate that tucidinostat provides survival benefits in patients with relapsed/refractory ATL in clinical practice and highlight key clinical factors for better outcomes.

P1/2, N=7, Terminated, Great Novel Therapeutics Biotech & Medicals Corporation | N=46 --> 7 | Trial completion date: Jan 2026 --> Jan 2025 | Recruiting --> Terminated; The overall profile does not support development for Hepatocellular Carcinoma

P1/2, N=44, Completed, The Netherlands Cancer Institute | Active, not recruiting --> Completed

P=N/A, N=200, Not yet recruiting, Cancer Institute and Hospital, Chinese Academy of Medical Sciences

P2, N=130, Not yet recruiting, Cancer Institute and Hospital, Chinese Academy of Medical Sciences

P1/2, N=47, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Jul 2025 --> Feb 2026

Compound 55 demonstrated good antitumor activity in vivo. Specifically, compound 55 combined with chidamide demonstrated a superior therapeutic effect over the first-line therapy RTX-CHOP in both the DEL and TP53 mutant DLBCL PDX tumor models.

Inhibiting histone deacetylase 3 abolishes niche softness-induced brain metastatic ability. Collectively, this study uncovers a previously unappreciated role of local niche softness within primary tumors in brain metastasis, highlighting the significance of primary tumor mechanical heterogeneity in metastatic organotropism.

P2, N=21, Active, not recruiting, The First Affiliated Hospital of Soochow University | Trial completion date: Aug 2025 --> Aug 2027 | Trial primary completion date: Dec 2024 --> Dec 2026

In addition, flexible molecular docking analysis, 200 ns MD simulation, and free energy landscape (FEL) analysis further established the importance of identified fingerprints in the modulation of HDAC3 inhibitory activity. This comprehensive analysis of structural variations among non-hydroxamate HDAC3i provides valuable insights, contributing to the design of potential non-mutagenic HDAC3i.

P2, N=33, Recruiting, The First Affiliated Hospital of Xiamen University | Trial completion date: Dec 2025 --> Dec 2027 | Trial primary completion date: Dec 2024 --> Dec 2026

P=N/A, N=400, Recruiting, Ruijin Hospital | Not yet recruiting --> Recruiting

P2, N=33, Recruiting, The First Affiliated Hospital of Xiamen University | Trial completion date: Dec 2025 --> Dec 2027 | Trial primary completion date: Dec 2024 --> Dec 2027

P2, N=30, Recruiting, Shanghai Jiao Tong University School of Medicine | Trial primary completion date: Jan 2025 --> Jan 2026

This study not only elucidates the biological function of lactylated METTL3 in tumor cells but also highlights its negative regulatory effect on cisplatin resistance. Additionally, it underscores the nonclassical functional mechanism of Tucidinostat as a HDAC inhibitor for improving the efficacy of cisplatin against TNBC.

Here, by screening a library of marketed drugs, we identified Chidamide had a strong binding affinity toward VISTA (KD = 5 nM) and blocked VISTA/PSGL-1 under acidic conditions, thereby significantly enhancing the function of CD8+ T cells and inhibiting the tumor growth in immunocompetent murine CT26 tumor model. This study represents the first discovery of Chidamide as VISTA/PSGL-1 blocker for cancer immunotherapy.

We demonstrated that HDAC inhibitors (Entinostat and Vorinostat) sensitize AML cells to ferroptosis both in vitro and in vivo. Our results suggest a novel therapeutic approach for AML, where combining HDAC inhibitors with ferroptosis inducers could exploit the disrupted iron metabolism in AML cells. This study highlights the potential of HDAC inhibitors to modulate iron metabolism pathways, offering new insights into the treatment of these malignancies.